Abstract
OBJECTIVE: Patients with features of systemic lupus erythematosus (SLE) who do not fulfill classification criteria can be designated as incomplete lupus erythematosus (ILE). This condition includes individuals with a high risk of progression to SLE. Treatment of ILE may reduce symptoms, severity, and incidence of SLE. METHODS: Hydroxychloroquine (HCQ) was chosen as an ILE intervention for a randomized, double-blind trial to determine whether the rate of accumulation of SLE features defined by the 2012 Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria could be reduced. ILE was defined as antinuclear antibody positivity with one to two additional criteria. Patients 15 to 49 years old were eligible. Randomization was 1:1 HCQ to placebo. Evaluations were at 3-month intervals over 24 months. Meeting SLICC classification sooner required exit. RESULTS: Participants (N = 187) were randomized at seven sites. After excluding 7 patients who met SLE classification at baseline when screening laboratory data were completed, 180 patients were analyzed: 92 receiving HCQ and 88 receiving placebo. Considering all these enrollees, 55 developed additional criteria. Of the 118 participants who exited early with SLE or who completed 24 months of evaluation, SLE classification developed in 24 (13.3%); another 24 developed additional criteria but did not meet classification. The rates of acquisition of SLICC criteria and progression to SLE were similar in the two groups (P = 0.72 and P = 0.98, respectively). Development of SLE was associated with new malar rash, oral ulcers, joint tenderness, or pleurisy (P < 0.04). CONCLUSION: Although the Study of Antimalarials in Incomplete Lupus Erythematosus (SMILE) did not show effects of HCQ on ILE progression, the results offer insights into SLE risk in the ILE population.